Dairy Consumption and Body Mass Index Among Adults: Mendelian Randomization Analysis of 184802 Individuals from 25 Studies

Author:

Huang Tao1234,Ding Ming4,Bergholdt Helle K M567,Wang Tiange3,Heianza Yoriko3,Sun Dianjianyi3,Frazier-Wood Alexis C8,Aslibekyan Stella9,North Kari E10,Voortman Trudy11,Graff Mariaelisa10,Smith Caren E12,Lai Chao-Qiang12,Varbo Anette613,Lemaitre Rozenn N14,de Jonge M Ester A L11,Fumeron Frédéric151617,Corella Dolores1819,Wang Carol A20,Tjønneland Anne21,Overvad Kim2223,Sørensen Thorkild I A2425,Feitosa Mary F26,Wojczynski Mary K26,Kähönen Mika2728,Renström Frida2930,Psaty Bruce M3132,Siscovick David S33,Barroso Inês343536,Johansson Ingegerd37,Hernandez Dena38,Ferrucci Luigi39,Bandinelli Stefania40,Linneberg Allan4142,Zillikens M Carola43,Sandholt Camilla Helene24,Pedersen Oluf2444,Hansen Torben24,Schulz Christina-Alexandra45,Sonestedt Emily45,Orho-Melander Marju45,Chen Tzu-An8,Rotter Jerome I46,Allison Mathew A47,Rich Stephen S48,Sorlí Jose V1819,Coltell Oscar1949,Pennell Craig E20,Eastwood Peter50,Hofman Albert11,Uitterlinden Andre G43,van Rooij Frank J A11,Chu Audrey Y51,Rose Lynda M51,Ridker Paul M5152,Viikari Jorma5354,Raitakari Olli5556,Lehtimäki Terho5758,Mikkilä Vera5659,Willett Walter C46061,Wang Yujie10,Tucker Katherine L62,Ordovas Jose M126364,Kilpeläinen Tuomas O24,Province Michael A26,Franks Paul W42965,Arnett Donna K66,Tanaka Toshiko39,Toft Ulla41,Ericson Ulrika45,Franco Oscar H11,Mozaffarian Dariush67,Hu Frank B46061,Chasman Daniel I516869,Nordestgaard Børge G61370,Ellervik Christina67172,Qi Lu3473,

Affiliation:

1. Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China

2. Epidemiology Domain, Saw Swee Hock School of Public Health, National University of Singapore, Singapore

3. Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA

4. Department of Nutrition, Harvard School of Public Health, Boston, MA

5. Department of Clinical Biochemistry, Naestved Hospital, Naestved, Denmark

6. Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

7. Department of Clinical Pharmacology, Copenhagen University Hospital Bispebjerg Frederiksberg, Copenhagen, Denmark

8. USDA/ARS Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX

9. Department of Epidemiology, School of Public Health, University of Alabama, Birmingham, AL

10. Department of Epidemiology, University of North Carolina, Chapel Hill, NC

11. Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands

12. Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA

13. Department of Clinical Biochemistry and the Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark

14. Department of Medicine, University of Washington, Seattle, WA

15. INSERM, UMR S 1138, Centre de Recherche des Cordeliers, Paris, France

16. University Paris Diderot, Sorbonne Paris Cité, UMR S 1138, Centre de Recherche des Cordeliers, Paris, France

17. Sorbonne Universités, UPMC University Paris 06, UMR S 1138, Centre de Recherche des Cordeliers, Paris, France

18. Department of Preventive Medicine and Public Health, University of Valencia, Valencia, Spain

19. CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain

20. School of Women's and Infants' Health, The University of Western Australia, Crawley, WA, Australia

21. Danish Cancer Society Research Center, Copenhagen, Denmark

22. Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark

23. Aalborg University Hospital, Aalborg, Denmark

24. Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

25. Department of Public Health Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

26. Department of Genetics, Washington University School of Medicine, St. Louis, MO

27. Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland

28. Department of Clinical Physiology Finnish Cardiovascular Research Center Tampere, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland

29. Genetic and Molecular Epidemiology Unit, Department of Clinical Sciences, Lund University, Malmö, Sweden

30. Department of Biobank Research, Umeå University, Umeå, Sweden

31. Kaiser Permanent Washington Health Research Institute, Seattle, WA

32. Cardiovascular Health Research Unit Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle, WA

33. New York Academy of Medicine, New York, NY

34. NIHR Cambridge Biomedical Research Centre, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK

35. University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK

36. Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK

37. Department of Odontology, Umeå University, Umeå, Sweden

38. Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD

39. Translational Gerontology Branch National Institute on Aging, Baltimore, MD

40. Geriatric Unit, Azienda Sanitaria Firenze (ASF), Florence, Italy

41. Research Centre for Prevention and Health, the Capital Region of Denmark, Copenhagen, Denmark

42. Department of Clinical Experimental Research, Rigshospitalet, Glostrup, Denmark

43. Department of Internal Medicine, Erasmus MC, University Medical Center, Rotterdam, the Netherlands

44. Faculty of Health Sciences, University of Aarhus, Aarhus, Denmark

45. Department of Clinical Sciences in Malmö, Lund University, Malmö, Sweden

46. Institute for Translational Genomics and Population Sciences, Departments of Pediatrics and Medicine, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA

47. Division of Preventive Medicine, Department of Family Medicine and Public Health, University of California San Diego, La Jolla, CA

48. Center for Public Health Genomics and Department of Public Health Sciences, University of Virginia, Charlottesville, VA

49. Department of Computer Languages and Systems, University Jaume I, Castellon, Spain

50. School of Anatomy, Physiology and Human Biology, The University of Western Australia, Western Australia, Australia

51. Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA

52. Division of Cardiovascular Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA

53. Division of Medicine, Turku University Hospital, Turku, Finland

54. Department of Medicine, University of Turku, Turku, Finland

55. Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland

56. Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland

57. Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland

58. Department of Clinical Chemistry Finnish Cardiovascular Research Center Tampere, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland

59. Department of Food and Environmental Sciences, University of Helsinki, Helsinki, Finland

60. Department of Epidemiology, Harvard School of Public Health, Boston, MA

61. Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA

62. Biomedical and Nutritional Sciences, Center for Population Health, University of Massachusetts Lowell, Lowell, MA

63. Department of Epidemiology and Population Genetics, Centro Nacional Investigación Cardiovasculares (CNIC), Madrid, Spain

64. Instituto Madrileño de Estudios Avanzados en Alimentación, Madrid, Spain

65. Department of Public Health and Clinical Medicine, Section for Medicine, Umeå University, Umeå, Sweden

66. Dean's Office, University of Kentucky, Lexington, KY

67. Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA

68. Division of Genetics, Brigham and Women's Hospital and Harvard Medical School, Boston, MA

69. Broad Institute of MIT and Harvard, Cambridge, MA

70. The Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen University Hospital, Copenhagen, Denmark

71. Department of Production Research and Innovation, Regionshuset, Soroe, Denmark

72. Department of Laboratory Medicine, Boston Children's Hospital and Harvard Medical School, Boston, MA

73. Tulane University Obesity Research Center, Tulane University, New Orleans, LA

Abstract

Abstract BACKGROUND Associations between dairy intake and body mass index (BMI) have been inconsistently observed in epidemiological studies, and the causal relationship remains ill defined. METHODS We performed Mendelian randomization (MR) analysis using an established dairy intake-associated genetic polymorphism located upstream of the lactase gene (LCT-13910 C/T, rs4988235) as an instrumental variable (IV). Linear regression models were fitted to analyze associations between (a) dairy intake and BMI, (b) rs4988235 and dairy intake, and (c) rs4988235 and BMI in each study. The causal effect of dairy intake on BMI was quantified by IV estimators among 184802 participants from 25 studies. RESULTS Higher dairy intake was associated with higher BMI (β = 0.03 kg/m2 per serving/day; 95% CI, 0.00–0.06; P = 0.04), whereas the LCT genotype with 1 or 2 T allele was significantly associated with 0.20 (95% CI, 0.14–0.25) serving/day higher dairy intake (P = 3.15 × 10−12) and 0.12 (95% CI, 0.06–0.17) kg/m2 higher BMI (P = 2.11 × 10−5). MR analysis showed that the genetically determined higher dairy intake was significantly associated with higher BMI (β = 0.60 kg/m2 per serving/day; 95% CI, 0.27–0.92; P = 3.0 × 10−4). CONCLUSIONS The present study provides strong evidence to support a causal effect of higher dairy intake on increased BMI among adults.

Publisher

Oxford University Press (OUP)

Subject

Biochemistry (medical),Clinical Biochemistry

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